Zelboraf 240 mg comprimidos recubiertos con pelicula

Prescribing Information for the Patient

Zelboraf 240Film-Coated Tablets

vemurafenib

Read this entire prescribing information carefully before starting to take this medication, as it contains important information for you.

• Keep this prescribing information, as you may need to refer to it again.
• If you have any questions, consult your doctor.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this prescribing information. See section 4.

Zelboraf is a cancer medication that contains the active ingredient vemurafenib. It is used to treat adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery.

It can only be used in patients who have a change (mutation) in the gene called “BRAF”. This change may cause the melanoma to develop.

Zelboraf acts on the proteins produced from this modified gene and slows down or stops the development of their cancer.

Do not takeZelboraf:

?if you are allergic to vemurafenib or any of the other ingredients of this medicine (listed in section 6). The symptoms of an allergic reaction may include swelling of the face, lips or tongue, difficulty breathing, rashes, or feeling dizzy.

Warnings and precautions

Consult your doctor before starting to take Zelboraf.

Allergic reactions

• You may have allergic reactions while taking Zelboraf, which can be severe.Stop taking Zelboraf and seek immediate medical help if you have any of the symptoms of an allergic reaction, such as swelling of the face, lips or tongue, difficulty breathing, rashes, or feeling dizzy.

Severe skin reactions

• You may have severe skin reactions while taking Zelboraf.Stop taking Zelboraf and consult your doctor immediately if you have a skin rash with any of the following symptoms: blisters on the skin, blisters or sores in the mouth, peeling of the skin, fever, redness or swelling of the face, hands or feet.

Previous history of cancer

• Inform your doctor if you have had a different type of cancer than melanoma, as Zelboraf may cause progression of certain types of cancer.

Reactions to radiation treatment

• Inform your doctor if you have received or are to receive radiation therapy, as Zelboraf may worsen the effects of radiation treatment.

Heart problems

• Inform your doctor if you have a heart problem,such as a heart rhythm disorder called “prolongation of the QT interval”.Your doctor will perform tests to check if your heart is working properly before and during your treatment with Zelboraf. If necessary, your doctor may decide to temporarily or permanently stop your treatment with Zelboraf.

Eye problems

• Your doctor should examine your eyes while you are taking Zelboraf.Consult your doctor immediately if you have pain, swelling, redness, blurred vision, or other changes in vision while on treatment.

Musculoskeletal and connective tissue disorders

• Inform your doctor if you notice an unusual thickening of the palms of your handsalong with finger stiffness or an unusual thickening of the soles of your feet that may be painful.

Inspect your skin before, during, and after treatment

• If you notice any changes in your skin during use of this medicine, please consult your doctor as soon as possible.
• Normally, during your treatment and for up to 6 months after, your doctor will inspect your skin to look for a type of skin cancer called “squamous cell carcinoma”.
• Normally, this lesion appears in sun-damaged skin, remains localized, and can be treated by surgery.
• If your doctor diagnoses this type of skin cancer, they will treat it or refer you to another doctor for treatment.
• Additionally, your doctor needs to inspect your head, neck, mouth, lymph nodes, and perform regular scans. This is a precautionary measure in case you develop squamous cell carcinoma inside your body. It is also recommended to have a gynecological examination (for women) and an anal examination before and after completing treatment.
• While taking Zelboraf, you may develop new melanoma lesions. These lesions are usually removed by surgery and patients continue with their treatment. The control of these lesions is carried out as indicated above for squamous cell carcinoma.

Kidney or liver problems

• Inform your doctor if you have kidney or liver problems. This may affect the activity of Zelboraf. Additionally, your doctor will perform some blood tests to monitor your liver and kidney function before starting treatment with Zelboraf and during treatment.

Sun protection

• If you are taking Zelboraf, you may become more sensitive to sunlight and experience severe sunburns. During treatment,avoid direct exposure of your skin to sunlight.
• If you are going to be exposed to the sun:
• use protective clothing, including your head and face, arms, and legs;
• use a lip balm and a broad-spectrum sunscreen (SPF 30 or higher), reapplying every 2-3 hours.
• This will help protect you from sunburns.

Children and adolescents

Zelboraf is not recommended for use in children and adolescents. The effects of Zelboraf in children under 18 years old are unknown.

Other medicines and Zelboraf

Before starting treatment, inform your doctor if you are using or have used recently or may need to use any other medicine.This is very important, as taking more than one medicine at a time may increase or decrease its pharmacological effect.

Please inform your doctor if you are taking:

• Medicines known to affect the way your heart beats:
• heart rhythm disorder medicines (e.g. quinidine, amiodarone)
• depression medicines (e.g. amitriptyline, imipramine)
• bacterial infection medicines (e.g. azithromycin, clarithromycin)
• nausea and vomiting medicines (e.g. ondansetron, domperidone).
• Medicines that are primarily eliminated by certain metabolic proteins called CYP1A2 (e.g. caffeine, olanzapine, theophylline) or CYP3A4 (e.g. some oral contraceptives) or called CYP2C8.
• Medicines that interfere with a protein called P-gp or BCRP (e.g. verapamil, cyclosporine, ritonavir, quinidine, itraconazole, gefitinib).
• Medicines that may be influenced by a protein called P-gp (e.g. aliskiren, colchicine, digoxin, everolimus, fexofenadine) or by a protein called BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).
• Medicines that stimulate certain metabolic proteins called CYP3A4 or the metabolic process called glucuronidation (e.g. rifampicin, rifabutin, carbamazepine, phenytoin or St. John's Wort).
• Medicines that strongly inhibit the metabolic protein CYP3A4 (e.g. ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, atazanavir).
• A medicine used to prevent blood clots called warfarin.
• A medicine called ipilimumab, another medicine for melanoma treatment. The combination of this medicine with Zelboraf is not recommended as it may increase liver toxicity.

If you are taking any of these medicines (or are unsure), please inform your doctor before taking Zelboraf.

Pregnancy and breastfeeding

• Use an appropriate contraceptive method during treatmentand for at least 6months after completing treatment.Zelboraf may reduce the effectiveness of some oral contraceptives. Inform your doctor if you are taking an oral contraceptive.
• Zelboraf is not recommended during pregnancy, unless your doctor considers that the benefits for the mother outweigh the risks for the baby. There is no information on the safety of Zelboraf in pregnant women. Inform your doctor if you are pregnant or intend to become pregnant.
• The components of Zelboraf are unknown to pass through breast milk. Breastfeeding is not recommended during treatment with Zelboraf.

If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor before using this medicine.

Driving and operating machinery

Zelboraf may have side effects that can affect your ability to drive or operate machinery. Fatigue or eye problems may be a reason for you not to drive.

Important information about some components of Zelboraf

This medicine contains less than 23 mg of sodium (1mmol) per tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

How many tablets should you take

• The recommended dose is 4 tablets twice a day (a total of 8 tablets).
• Take 4 tablets in the morning. Then take 4 tablets at night.
• If you notice any adverse effects, your doctor may reduce your dose to continue your treatment. Always take Zelboraf as directed by your doctor.
• If you experience vomiting, continue taking Zelboraf as you normally do and do not take an additional dose.

Take your tablets

• Do not take Zelboraf regularly on an empty stomach.
• Swallow the tablets whole with a glass of water. Do not chew or crush the tablets.

If you take more Zelboraf than you should

If you take more Zelboraf than you should, inform your doctor immediately. Taking more Zelboraf may increase the likelihood and severity of adverse effects. No cases of overdose with Zelboraf have been observed.

If you forget to take Zelboraf

• If you forget to take a dose and more than 4 hours remain until the next dose, take the missed dose as soon as you remember. Take the next dose according to the usual schedule.
• If less than 4 hours remain until the next dose, skip the missed dose and continue taking Zelboraf according to the usual schedule.
• Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Zelboraf

It is essential to take Zelboraf for the prescribed treatment period.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe allergic reactions

If you experience:

• Swelling of the face, lips, or tongue
• Difficulty breathing
• Rash
• Sensation of fainting.

Inform your doctor immediately. Do not take more Zelboraf tablets until you have informed your doctor.

Worsening of side effects by radiation in patients treated with radiation therapy before, during, or after treatment with Zelboraf may occur. This can happen in the area treated with radiation, such as the skin, esophagus, gallbladder, liver, rectum, and lungs.

Inform your doctor immediately if you notice any of the following symptoms:

• Rash, blisters, peeling, or discoloration of the skin
• Difficulty breathing, which may be accompanied by cough, fever, or chills (pneumonitis)
• Difficulty or pain swallowing, chest pain, burning, or acid reflux (esophagitis).

Please inform your doctor if you notice any change in your skin as soon as possible.

The following side effects are listed in order of frequency:

Very common (may affect more than 1 in 10 patients):

• Rash or skin irritation, itching, dry or scaly skin
• Skin disorders, including warts
• A type of skin cancer (squamous cell carcinoma)
• Syndrome palmoplantar (i.e., redness, peeling of the skin, or blisters on hands and feet)
• Sunburn, increased sensitivity to sunlight
• Loss of appetite
• Headache
• Changes in taste perception
• Diarrhea
• Constipation
• Nausea, vomiting
• Hair loss
• Muscle or joint pain, musculoskeletal pain
• Pain in the extremities
• Back pain
• Feeling of fatigue (fatigue)
• Dizziness
• Fever
• Swelling, usually in the legs (peripheral edema)
• Cough

Common (may affect up to 1 in 10 patients):

• Types of skin cancer (basal cell carcinoma, new primary melanoma)
• Thickening of the tissues under the palm of the hand that may cause finger stiffness; if severe, it may be disabling
• Inflammation of the eye (uveitis)
• Bell's facial paralysis (a type of facial paralysis that is often reversible)
• Sensation of tingling or burning of hands or feet
• Joint inflammation
• Inflammation of the hair follicle
• Weight loss
• Inflammation of blood vessels
• Problems with nerves that may cause pain, loss of sensation, and/or muscle weakness (peripheral neuropathy)
• Changes in liver test results (increased ALT, alkaline phosphatase, and bilirubin)
• Changes in heart activity (prolongation of the QT interval)
• Inflammation of subcutaneous fat
• Abnormal results in blood tests for kidney function (increased creatinine)
• Changes in liver test results (increased GGT)
• Decreased white blood cell count (neutropenia)
• Low platelet count (thrombocytopenia)
• Mouth pain or ulcers, inflammation of mucous membranes (stomatitis)

Uncommon (may affect up to 1 in 100 patients):

• Allergic reactions that may include swelling of the face and difficulty breathing
• Blockage of blood flow to a part of the eye (retinal venous occlusion)
• Inflammation of the pancreas
• Changes in liver test results or liver damage, including severe liver damage that prevents the liver from functioning properly
• A type of cancer (non-cutaneous squamous cell carcinoma)
• Thickening of deep tissues under the sole of the foot that could be

incapacitating if severe

Rare (may affect more than 1 in 1,000 patients):

• Progression of certain pre-existing cancers with RAS mutations (Chronic Myelomonocytic Leukemia, Pancreatic Adenocarcinoma)
• A severe skin reaction characterized by rash accompanied by fever and inflammation of internal organs such as the liver and kidneys
• Inflammatory diseases that primarily affect the skin, lungs, and eyes (sarcoidosis)
• Types of kidney damage characterized by inflammation (acute interstitial nephritis) or damage to the kidney tubules (acute tubular necrosis)

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.

By reporting adverse reactions, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and in the blister pack after CAD. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from moisture.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition ofZelboraf

• The active ingredient is vemurafenib. Each film-coated tablet contains 240milligrams (mg) of vemurafenib (in the form of vemurafenib co-precipitate and hypromelosa acetate succinate).
• The other components are:
• Tablet core: anhydrous colloidal silica, sodium croscarmellose, hydroxypropyl cellulose, and magnesium stearate
• Film coating: red iron oxide, macrogol 3350, polyvinyl alcohol, talc, and titanium dioxide.

Appearance of the product and contents of the pack

Zelboraf 240mg film-coated tablets are white pink to slightly orange in color. They are oval-shaped with the inscription “VEM” engraved on one of the faces.

They are presented in a blister pack of aluminum troquel in packs of56x1tablets.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible for manufacturing

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639

Grenzach-Wyhlen

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/